Systematic review and meta-analysis of birth weight and perfluorohexane sulfonate exposures: examination of sample timing and study confidence

We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.We detected a -7.9 g (95% CI -15.0 to -0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (beta=-10.0 g; 95% CI -21.1 to 1.1) showed larger deficits than 12 high (beta=-6.8 g; 95% CI -16.3 to 2.8) and 4 low confidence studies (beta=-1.5 g; 95% CI -51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (beta=-3.9 g; 95% CI -17.7 to 9.9) than 5 post-partum studies (beta=-28.3 g; 95% CI -69.3 to 12.7) and 12 early sampling studies (beta=-7.6 g; 95% CI -16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.